Apparatus for tissue stimulation

ABSTRACT

Mathematical functions such as recursive autoregression models which include parameters are used for defining the heart signal and any signals disturbing the heart signal, such as polarization signals. By registering, during a predetermined time interval, the electrode signal for determining the parameters for one or more different mathematical functions, the parameters can be used on their own or in combination to determine the activity of the heart, i.e., whether the registered electrode signal corresponds to a stimulated, spontaneous or absence of heart activity.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The invention relates to an apparatus for tissue stimulation, and inparticular a heart pacemaker, for detection of a response to astimulation pulse when the measured signal is corrupted by an electrodepolarisation artefact.

2. Description of the Prior Art

It is desirable that pacemakers have a low energy consumption such thatthe battery lasts longer. To enable the reduction of the energyconsumption it must be clear whether there has been a capture (=a heartcontraction/evoked response) or not at the prevailing stimulationvoltage. For a proper detection of capture, it is important that theartefact at stimulation, i.e. the polarization voltage, is not so largethat it is detected as capture. If the polarization voltage could beeliminated the detection of capture would be easier and more reliable.

U.S. Pat. No. 4,543,956 discloses a system for detecting the evokedresponse in which the polarization is neutralized using a biphasicwaveform technique whereby a compensating current pulse is transmittedin the opposite direction from the stimulating current pulse. However,the compensating current pulse is often emitted very close in time tothe stimulation pulse, the recharge pulse thus tending to mask theelectrical response from the heart and in particular in the case where aunipolar electrode is used.

U.S. Pat. No. 5,431,693 discloses a pacemaker for detecting capturebased on the observation that the non-capture potential is exponentialin form and the evoked response potential, while generally exponentialin form, has one or more small-amplitude perturbations superimposed onthe exponential waveform and whereby the perturbations are enhanced forease of detection. The perturbations involve relatively abrupt slopechanges, which are enhanced by processing the waveform signaldifferentiation. Abrupt slope changes in the second derivative are usedto detect morphological features indicative of capture which areotherwise difficult to discriminate.

U.S. Pat. No. 5,165,405 relates to a pacemaker comprising means foracquiring the curve of the polarisation phenomenon by stimulating thetissue with a stimulation energy lying below the stimulation threshold,so that the electrical potential signal in the tissue subsequentlyacquired by the detector means corresponds to the polarization phenomenaproduced by the stimulation attempt without these having an evokedresponse of the tissue superimposed thereon. By regularly updating thepolarisation signal, an optimal compensation of the polarisationcomponents contained in the acquired electrical potential signal isachieved for the purpose of detecting an evoked response.

U.S. Pat. No. 5,417,718 defines a pacemaker that includes a so calledAutocapture™ system for automatically maintaining the energy of thestimulation pulses generated by the pacemaker at a predetermined levelsafely above that needed to effectuate capture. The Autocapture™ systemperforms its function by comparing the electrical evoked response of theheart following the generation of a stimulation pulse to a polarizationtemplate determined by a capture verification test. During the captureverification test, the Autocapture™ system causes the pacemaker to firstgenerate a series of pacing pulse pairs. The first pulse of the pair hasa high energy to ensure capture. The second pulse of the pair is of theprescribed stimulation energy. The signal corresponding to the secondpulse (which signal is dominated by polarization information) is sensedthrough a sensing circuit having a specified sensitivity setting. Suchsignal is stored as the polarization template corresponding to thatparticular energy and sensitivity setting. In view of the leadpolarization signal not being easily characterised, due to it being acomplex function of e.g. the lead materials, lead geometry, tissueimpedance, stimulation energy, most of which are continuously changingover time, the capture verification test creates a table of polarizationtemplates as a function of sensitivity settings for a particularstimulation energy.

SUMMARY OF THE INVENTION

It is an object of the invention to provide an apparatus for tissuestimulation wherein the reaction of the tissue to the stimulation isreliably detected independently of the presence of a polarizationvoltage.

The invention is embodied in an apparatus for tissue stimulationachieving a reliable capture detection which would make it possible touse different pacemakers with one and the same electrode, and inparticular a unipolar electrode. This would be highly favorable forpatients who have an already implanted and well functioning unipolarelectrode, but who are in need of a new pulse generator due to e.g.battery end of life (EOL) and/or in need of a more modern pacemaker e.g.comprising the Autocapture™ function.

Due to a faster detector unit response, another advantage would be thepossibility of more reliably reducing the stimulation voltage needed forcapture (Autocapture™ function).

These advantages are achieved in accordance with the invention, which isbased on the observation that a detected heart signal and any signaldisturbing the detected heart signal, e.g. a polarisation signal, can beapproximated by mathematical functions. These functions compriseparameters. These parameters are different for each of thesemathematical functions depending on if the stimulation pulse has causedcapture or not. By letting the pacemaker during a predetermined timeinterval register the electrode signal for determining the parametersfor one or more different mathematical functions, one or severalparameters can be used to determine the activity of the heart, i.e. ifthe registered electrode signal corresponds to capture or non capture.

In a preferred embodiment the mathematical functions may be more or lessdirect or indirect and hence, an autocorrelation calculation may beneeded before the determination of the parameters. A regression analysismay also be appropriate. Moreover, by using a recursive autoregressionmodel the parameters for the detected signal with respect to thecorresponding stimulation pulse may be used as a means for detecting theevoked response. Furthermore, a Kalman filter may be used to determinethe parameters, especially if the signals have properties knownbeforehand.

In a preferred embodiment the parameters are continuously determinedduring a time interval of 10 ms to 120 ms after a stimulation pulse andevaluated in a window from 15 ms to 120 ms or 50 to 100 ms. In anotherpreferred embodiment the parameters are determined and evaluated onlyonce at a point between 50 and 100 ms and preferably at 60 ms after thestimulation pulse.

DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic block diagram of an apparatus for tissuestimulation, in the form of a hear pacemaker, consturcted in accordancewith the principles of the present invention.

FIG. 2A shows a unipolar evoke response measured between the tip in aventricle and a pacemaker can, according to an embodiment of theinvention.

FIG. 2B shows the polarization modeled by three exponential decays, aconstant negative level and a positive linear trend according to anembodiment of the invention.

FIG. 2C shows the combined measured signal of evoked response andpolarization of FIG. 2A and FIG. 2B, respectively, according to anembodiment of the invention.

FIG. 3A shows two parameters as a function of time calculated using aKalman filter algorithm and the signal from FIG. 2A, according to anembodiment of the invention.

FIG. 3B shows two parameters as a function of time calculated using aKalman filter algorithm and the signal from FIG. 2B, according to anembodiment of the invention.

FIG. 3C shows two parameters as a function of time calculated using aKalman filter algorithm and the signal from FIG. 2C, according to anembodiment of the invention.

FIG. 4A shows the normalized first parameter for the three differentsignals in FIGS. 2A through 2C, according to an embodiment of theinvention.

FIG. 4B shows the second normalized parameter for the three differentsignals in FIGS. 3A through 3C, according to an embodiment of theinvention.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

As a preferred embodiment of the device of the invention, FIG. 1 showsthe block circuit diagram of a heart pacemaker 1 for tissue stimulation,in this case the stimulation of a heart 2. The heart pacemaker 1includes a stimulation pulse generator 3 that has its output sideconnected via an electrode line 4 to an electrode 5 applied in theventricle of the heart 2 for stimulating the heart 2 with stimulationpulses. Of course, even if the preferred embodiment shows the electrodeto be located in the ventricle, the invention also covers the electrodebeing located in the atrium. The stimulation pulse generator 3 can beactivated to deliver a stimulation pulse via a control line 6, which isconnected to a corresponding output of a control unit 7. The stimulationpulse generated by the stimulation pulse generator 3 may be anyone ofthe stimulation pulses known to the skilled person. The duration of therespective stimulation pulse as well as the setting of the amplitudesetting of the stimulation pulses may also be set via the same line 6.In the illustrated preferred embodiment, the control unit 7 is amicroprocessor to which a read-only memory (ROM) 8 and a random accessmemory (RAM) 9 are assigned, these being connected to the microprocessor7 via data lines, address lines, as well as via a write-read switchingline in the case of the random memory 9. A program that executes allfunctions of the heart pacemaker 1 via the microprocessor 7 is stored inthe read-only memory 8. Therein mathematical functions approximating theheart signal and any signal disturbing the heart signal, e.g.polarization signals, are stored to be used by the control unit 7 fordetermining and evaluating if a detected signal corresponds tostimulated, spontaneous or lack of activity of the heart.

The heart signal may be approximated by the mathematical functions

A/(t−D)

where A and D are parameters or

C*t/(E+t²)

where C and E are parameters.

A polarization signal may be approximated by the mathematical function

B*exp (−t/T)

where B and T are parameters

in accordance with the results of the Master Thesis at the RoyalInstitute of Technology, Stockholm, with the title “A Model of thePolarisation Dependent Impedance” by Åsa Uhrenius, published December1995.

Yet another mathematical function may be a recursive autoregressionmodel. In an ideal situation the parameters are constants for the wholeperiod of the detected signal. However, due to the signal only beingdetected during a predetermined time interval and for a limited quantityof data, the parameters are substantially constant during thepredetermined time interval, i.e. the parameters are to a certain degreetime-dependent.

The pacemaker 1 also includes a telemetry unit 13 connected to themicroprocessor 7 for programming and for monitoring functions of thepacemaker 1 on the basis of data exchange with an external programmingand monitoring device (not shown).

By means of the telemetry unit 13 the parameters of the mathematicalfunctions are preferably determined at the implantation so that they areadapted to the patient and thereafter stored in the ROM 8. Themathematical functions may also be chosen and stored in the ROM 8 bymeans of the telemetry unit 13 at implantation or they may be stored atthe time of fabrication of the pacemaker 1.

In order to be able to acquire the reaction of the heart, e.g. given astimulation, the heart pacemaker 1 contains a detector unit 10 which hasan input side connected via the electrode line 4 to the electrode 5 foracquiring the electrical potential in the heart tissue. This arrangementis simple because only a single electrode 5 is required both forstimulating the heart 2 and for acquiring the reaction thereof. However,because the tissue is so highly polarized in the immediate region of theelectrode 5 after every stimulation, the polarization voltage maysuperimpose the evoked response of the heart 2 to the degree of makingit unrecognizable. Of course, another preferred embodiment of the deviceof FIG. 1 also allows the employment of a separate stimulation electrodeand measuring electrode for respectively stimulating the tissue and foracquiring the evoked response.

The curve of the electrical potential in the heart tissue acquired bythe detector unit 10 and corresponding to electrical heart activity issupplied to an input of a signal processor 11. The signal processor 11acquires a quantity of data corresponding to the curve of the electricalpotential in the heart tissue detected by the detector unit 10. Thesignal processor 11 may contain means for pre-processing the by thedetector unit 11 detected signal, e.g. means for band-pass filtering thedetected signal. Thereafter the parameters are determined before theparameters are sent to the evaluation circuit 12. The parameters mayafter the quantity of data has been acquired be determined either onlyonce before being sent to the evaluation circuit 12 or they may bedetermined continuously during the predetermined time interval duringwhich the quantity of data is acquired and consequently, the more dataacquired the more reliable the determination of the parameters.

The processing of the signal and evaluation of parameter values may beperformed as mentioned below:

The signal from the electrodes is amplified and band pass filteredbefore further processing. Such a bandpass filter should not influencesignals that are sought for further means a high pass filter should beused having a frequency limit in the order of 3-0.1 Hz to avoid DC-levelor very slow changing signals. A low pass limitation to attenuate highfrequency interference may have a frequency limit in the order of1000-200 Hz.

The filtered signal is quantified in an analog to digital (AD) converterusing a sampling rate in the order of 200-800 samples/second. The valuesare stored in the RAM 9. The stored values are then utilized in acomputing process to determine the parameter values characterizing anidealized signal, the idealized signal being constructed from simplemathematical functions as mentioned above. The parameter valuesbelonging to the idealized function are determined so that there is abest adaptation or least error compared to the real measured signal.

The computed parameter values are used to discriminate between captureand non capture. If one or several parameter values are within somepredetermined limits, then this is used as an indicator of capture. Theopposite is also valid. These limits are determined at the time ofimplantation.

If the quantity of stored values is equal to the quantity of parametersfor each function the parameter values can be determined by solving anequation system. For example, the function A/(t−D) requires two datapoints Z₁ and Z₂ measured at time points t₁ and t₂ after stimulation todetermine the two parameters A and D.

There is always a small influence from interfering sources, measurementaccuracy, etc. which may give inaccurate determination of theparameters. Therefore a longer sequence of measured values is preferablyused. The parameters can then not be solved from a simple equationsystem. There are several methods to solve so called over estimatedequations where the quantity of known values exceeds the quantity ofunknown. There are matrix methods, which require some computing.

A suitable method is iterative solving, whereby the difference isminimized between the measured values and the values of the idealisedfunction.

The function F gives values F_(i) at time points t_(i) for a givenparameter set. Z_(i) are the measured values at corresponding timepoints. In the least squares method the “error” function with the“error” value E is determined: E=_(1;N)(F_(i)−Z_(i))².

Then one or some of the parameter values are changed with small stepsand the “error” function is determined again. Thereby one has thepossibility to get the parameter values through iterative steps thatminimize the error value. The sought parameter values are thosedetermined by iteration and consequently they will be used forindication of heart occurrence.

During iteration a simplified requirement may be to stop the computingwhen the error is below a predetermined limit instead of totallyeliminating the error value.

Another simplification that may be used is a simpler error function:E=_(1;N)(|F_(i)−Z_(i)|), where |F_(i)−Z_(i)| means the absolute value ofFi−Zi. Then must be used to avoid other problems resulting from noise,special shape of the signals, etc. Problems arising during computationmay be reduced by averaging, value limitations, etc.

To bring down the number of iterations it is essential to have properlypredetermined starting values of the parameters, to have a suitable stepsize when varying the parameters and to have good stop criteria for theiterations.

The least squares method is well known to the person skilled in the art.

By means of the Kalman filter the determination of the parameters isfaster and more reliable, since known properties of the heart signalsand signals disturbing the heart signals are used. The Kalman filter isa mathematical process whereby properties which were known before themeasurement was started are taken into account. It is especiallysuitable if the registered information, to be taken into accounttogether with the properties known beforehand, is limited or badlydetermined. In this case, either the general appearance of the heartsignal or the polarisation signal are known beforehand or they may bedetermined by repeated registration. Hence, it is known what thepreferred parameters should be for capture and non capture. Theparameter's distribution is used together with the Kalman filter so asto more reliably determine the parameters for the latest registeredsignal and thereafter letting the evaluation circuit 12 decide ifcapture or non capture activity or lack of activity prevails based onthe value of one or more parameters.

The parameters as a function of time will then characterise the measureddetected signal corresponding to stimulated, spontaneous or lack ofheart activity 1. There will be significant differences between theparameters as a function of time if the polarisation signal is presentin the detected signal, as can clearly be seen from FIGS. 3 and 4.

Less advanced algorithms for estimating the parameters of themathematical function, e.g. a recursive autoregression model, may beused, e.g. the least square method. The Kalman filter algorithm as wellas other less advanced algorithms, which are used for determining theparameters defining the mathematical functions, are well known in theart of signal processing. However, until now these algorithms have notbeen used in the field of pacemaker technology, and in particular notfor reliably detecting capture.

The identified parameters as a function of time are then fed to anevaluation circuit 12 wherein a logical signal capture/no capture isgenerated by evaluating the parameters as a function of time after theend of the stimulation pulse. The parameters are preferably evaluated bycomparing them to predetermined parameters that have been determined atimplantation for the particular mathematical functions stored in the ROM8 for defining the heart signal and any signal disturbing the heartsignal. The evaluation circuit 12 need not be further described, sinceit would be well-known to the skilled person how to build such acircuit. However, it may be build of conventional linear processingcircuits combined with threshold detection and logical circuits.

Depending on the electrode placement and on the type of electrode used,unipolar or bipolar electrode, the heart response to a stimulation pulsearrives after 2 to 15 ms and 20 to 40 ms respectively. In a preferredembodiment the parameters are continuously determined during a timeinterval of 10 ms to 120 ms after a stimulation pulse and evaluated in awindow from 15 ms to 120 ms or 50 to 100 ms. In another preferredembodiment the parameters are determined and evaluated only once at apoint between 50 and 100 ms and preferably at 60 ms after thestimulation pulse.

Experiments have shown that the parameters are more or less equal up tothe break point of 30 ms, which can be seen from FIGS. 4A and 4B, thusindicating that it is preferable to determine the parameters as afunction of time starting 15 ms after the end of the stimulation pulse.However, detection may start at 30 ms after the end of the stimulationpulse. The resulting logical signal capture/no capture from theevaluating circuit 12 is an output corresponding to a, by the controlunit 7 for the detector unit 10, pre-selected detection window.

The detector unit 10, the signal processor 11 and the evaluation circuit12 may be activated via control lines respectively, which are connectedto a corresponding output of the control unit 7. Of course, thepreferred embodiment of the device as shown in FIG. 1 also allows themicroprocessor 7 to perform the functions of the detector unit 10, thesignal processor 11, and the evaluation circuit 12.

FIGS. 2 to 4 show an example of how the three different possible signalsof FIGS. 2A, 2B and 2C are distinguished from each other by determiningthe time-dependent parameters of a mathematical function such as arecursive autoregression model using a Kalman filter.

FIGS. 2A, 2B and 2C show respectively a unipolar evoked responsemeasured between the tip in a ventricle and a pacemaker can, thepolarization modelled by three exponential decays, a constant negativelevel and a positive linear trend, and the combined measured signal ofevoked response and polarization of FIG. 2A and FIG. 2B respectively. Asis clear from FIG. 2B and FIG. 2C it is quite difficult to distinguishthe combined signal of evoked response and polarization from the purepolarization signal.

FIGS. 3 and 4 show an example using two time-dependent parameters forcharacterising the signals. The proposed predetermined model is arecursive autoregression model and the parameters thereof are determinedusing the Kalman filter algorithm. As already mentioned, less advancedalgorithms may be used. Furthermore, one parameter or more may be usedfor best defining the recursive autoregression model. However, two tofour parameters are preferred for optimising the reliability of themodel and the time needed for determining the parameters, since thefaster and the more reliable logical signal capture/no capture isdetermined, the faster and the more reliable the control unit 7 canadapt the control signals to the stimulation pulse generator 3 to theprevailing situation. So as to obtain a reliable result, the signalprocessor 11 preferably samples the curve obtained with the detectorunit 10 at a rate of 1000 Hz.

FIGS. 3A, 3B and 3C thus show the three pairs of parameters obtainedfrom the three signals by using the proposed model. The onlypre-processing was to remove the average level from the combinedmeasured signal.

It is also possible to normalize the parameters to a peak-to-peak valueof one unit and let the time-dependent parameters start at zero at thebeginning of a predefined detection window. FIGS. 4A and 4B show thenormalised first and second parameters for the three different signalsin FIG. 2A to 2C, the detection window being defined to start 15 msafter the end of the stimulation pulse. At the time of 200 ms, in FIG.4A the curves are from bottom to top: polarisation only 20, evokedresponse only 21, and combined measured signal 22; and in FIG. 4B:polarisation only 23, combined measured signal 24, and evoked responseonly 25. From FIGS. 4A and 4B it is clear that since the signals aresubstantially equal until 30 ms, the evaluation circuit 12 may beactivated shortly before the break point 30 ms for determining thelogical signal capture/no capture.

In the example shown in FIGS. 2 to 4, the signal processing is startedimmediately after the stimulation pulse at time=0 and continued over along period of time. A preferred signal processing window would be inthe time interval of 20 ms to 120 ms after the end of the stimulationpulse. The evaluation window of the evaluation circuit 12 may be awindow inside the signal processing window or equal to it, e.g. 25 ms to120 ms after the stimulation pulse. However, the signal processing mayalso be started at 60 ms after the end of the stimulation pulse.

One skilled in the art will appreciate that the present invention can bepractised by other than the described embodiments, which are presentedfor purposes of illustration, and the present invention is limited onlyby the claims which follow.

We claim as our invention:
 1. An apparatus for tissue stimulationcomprising a pulse generator which generates stimulation pulses, anelectrode connected to said pulse generator and adapted for deliveringsaid stimulation pulses in vivo to tissue, a detector which acquires anelectrical signal corresponding to an electrical potential at saidtissue during a predetermined time interval following a deliveredstimulation pulse, a determination unit which determines a value of atleast one parameter of a predetermined mathematical function, whichproduces a best adaptation of said predetermined mathematical functionto said electrical signal during said predetermined time interval, andan evaluation unit which compares the at least one parameter with apredetermined corresponding parameter range and which generates a signalindicative of a result of said comparison.
 2. An apparatus as claimed inclaim 1, wherein said mathematical function is A/(t−D) where A and D areparameters and t is time.
 3. An apparatus as claimed in claim 2 whereinsaid determination unit determines the parameters using two data pointsof said electrical signal.
 4. An apparatus as claimed in claim 1,wherein said mathematical function is C*t/(E+t²) where C and E areparameters and t is time.
 5. An apparatus as claimed in claim 1, whereinsaid electrical signal is a polarization signal and wherein saidmathematical function is B*exp(−t/T) where B and T are parameters and tis time.
 6. An apparatus as claimed in claim 5 wherein saiddetermination unit continuously determines the parameter during a timeinterval of 10 ms to 120 ms after a stimulation pulse.
 7. An apparatusas claimed in claim 6, wherein said evaluation unit evaluates said atleast one parameter only once at a point between 50 and 100 ms after thestimulation pulse.
 8. An apparatus as claimed in claim 7, wherein saidevaluation unit evaluates said at least one parameter at 60 ms after thestimulation pulse.
 9. An apparatus as claimed in claim 6, wherein saidevaluation unit evaluates said at least one parameter during at timewindow from 15 ms to 120 ms after the stimulation pulse.
 10. Anapparatus as claimed in claim 1, wherein said mathematical function is arecursive autoregression model.
 11. An apparatus as claimed in claim 1wherein said determination unit determines said at least one parameterusing the last squares method.
 12. An apparatus as claimed in claim 1wherein said determination unit determines said at least one parameterusing a Kalman filter.
 13. An apparatus as claimed in claim 1 whereinsaid signal generated by said evaluation unit indicates capture if saidat least one parameter falls within said corresponding parameter range,and indicates non-capture if said at least one parameter does not fallwithin said corresponding parameter range.